1. Field of the Invention
The present invention relates to compositions and methods for improved vaccines. In particular embodiments, the compositions and methods relate to xenoantigens, chemically modified antigens, antigens in conjunction with Th epitopes, dendritic cells loaded with antigens, immunoconjugates or fusion proteins comprising dendritic cell targeting antibodies attached to antigens and/or dendritic cell targeting lentiviral vectors expressing antigens. The vaccines are of use for therapy of a wide variety of diseases, including but not limited to cancer, autoimmune disease, immune dysfunction disease, metabolic disease, neurological diseases such as Alzheimer's and cardiovascular disease.
2. Related Art
Therapeutic vaccination against cancer is an important modality complementing current standard therapies, and may lead to long-term control of cancer. Numerous strategies are in development in an attempt to achieve better effectiveness, but except for the recent advent of vaccines against HPV, the long effort to produce a cancer vaccine has not succeeded.
Two major categories of tumor-related proteins can be exploited as potential antigens for cancer vaccines: tumor-specific antigens (TSAs) (Srivastava and Old, Immunol Today 9:78-83, 1988; Melief et al., Cold Spring Harbor Symp Quant. Biol 65:597-803, 1989; Hislop et al., Annu Rev Immunol. 25:587-617, 22007) and tumor-associated antigens (TAAs) (Dalgleish and Pandha, Adv Cancer Res 96:175-90, 2007; Finn, NEJM 358:2704-15, 2008). TSAs are molecules unique to cancer cells, such as the products of mutated normal cellular genes, viral antigens expressed on tumor cells, endogenous human retrovirus activated and expressed in cancer cells (Takahashi et al., J Clin Invest 118:1099-1109, 2008), and a recently identified placenta-specific antigen that is not found in any adult normal somatic tissue but highly expressed in a variety of tumor types, particularly in breast cancer (Chen et al., Beijing Da Xue Xue Bao 38:124-27, 2006; Koslowski et al., Cancer Res 67:9528-34, 2007; Old, Cancer Immunity 7:19, 2007). TAAs are molecules shared, but differently expressed, by cancer cells and normal cells.
Although TSAs are the ideal targets for immunotherapy and vaccination, the fact that they are expressed only on individual patients' cancer cells or small subsets of tumors would require the development of personalized therapy for individual patients, thus limiting their wide application (Baxevanis et al., Cancer Immunol Immunother 58:317024, 2009). As for TAAs, which are largely self-antigens (self-Ags) already tolerized by the immune system through a tightly controlled process of negative selection in the thymus (Kruisbeek and Amsen, Curr Opin Immunol 8:233-44, 1996; Stockinger, Adv Immunol 71:229-65, 1999) or peripheral tolerization, the major challenge is to induce a strong immune response directed selectively against cancer cells.
A need exists in the field for new approaches to vaccines of use for cancer treatment and/or prevention, capable of inducing a strong immune response against cancer cells and of wide application.